Cancer Therapeutics

The overall goal of the Cancer Therapeutics (CT) Research Program is to translate UNMCCC science into
clinical and community interventions that improve cancer prevention, treatment, and survival in our catchment area—the state of New Mexico—and across the nation. CT accomplishes this through continued innovation in the development and clinical translation of cancer therapies, and the reverse translation of results from clinical interventions to inform mechanistic studies, thus ensuring that the development of next-generation regimens will be relevant to residents in our catchment area.

CT collaborates with:

• the Cellular and Molecular Oncology (CMO) Program to identify and prioritize molecular targets for
  therapeutic interventions;
• the Cancer Control and Population Science (CCPS) Program to implement new strategies for cancer prevention;
• the UNMCCC disease-focused Clinical Working Groups (CWG) and CPDM to develop innovative clinical trials based on center science; and
• CRTECC to train the next generation of cancer researchers and clinicians.

The CT translational pipeline currently includes:

1. small-molecule discovery, development and trials,
2. design and development of nanoparticle-based cancer immunotherapeutics,
3. translation of new agents and drug combinations, based on artificial intelligence methodologies, to clinical and community interventional trials at UNMCCC and nationally, and
4. development of a clinical trials menu to meet the needs of patients in our catchment area, supported by an NCI NCORP grant.

CT’s Specific Aims are to:

1. Employ cutting-edge technologies and machine learning to identify genetic vulnerabilities and develop new therapeutic agents;
2. Conduct mechanistic studies that will advance the development of novel therapeutics and clinical interventions; and
3. Translate our discoveries to clinical and community interventions aligned with the  needs of our catchment area.
   
   

Aim 1: Employ cutting-edge technologies and machine learning to identify genetic vulnerabilities and develop new therapeutic agents. To promote inter-programmatic collaborations with CMO aimed at identifying transformative treatment strategies for clinical translation, we broadened the scope of our discovery aim. Small-molecule screening efforts have been advanced through a collaborative agreement with the Sanford Burnham Prebys Medical Discovery Institute’s Center for Chemical Genomics. The inclusion of structural biology and new inter-institutional discovery initiatives will enable ultra-high-throughput screening to identify and develop new small-molecule inhibitors for unique targets. This approach is complemented by the innovative application of artificial intelligence models that account for patient heterogeneity to discover and personalize new cancer regimens. Artificial intelligence-based strategies to refine and accelerate biomarker discovery will further inform the design of precision clinical trials. Finally, the launch of a fully integrated informatics system and data warehouse, Cancer Research Integrated Informatics System (CRIIS), that combines longitudinal patient data with clinical-grade genomic data will present an opportunity for collaboration with CCPS and allow us to identify interventions to reduce the cancer burden and improve outcomes in our catchment area.

Research Accomplishments and Scientific Highlights:

• Artificial intelligence
• Diagnostic cancer imaging
• Targeted therapeutics (also Aim 2 and 3)
• Discovery of GPER/ER-selective ligands and advancement to phase II/III trials (also Aims 2 and 3)

Aim 2: Conduct mechanistic studies that will advance the development of novel therapeutics and
clinical interventions. We have prioritized the collection and clinical annotation of patient specimens to support mechanistic studies and biomarker development in order to design and advance new precision therapeutics. Leveraging innovative cancer models, including humanized and autologous patient-derived xenografts, has enabled investigators to advance silicified cancer-cell-based immune strategies, studies of steroid hormone effects in the tumor microenvironment, and cutting-edge approaches to oncolytic viral cancer therapy. Multi-PI grants led by CT members, and leadership in national consortia, expand the impact of the translational studies led by UNMCCC investigators, e.g., the launch of the phase-III national clinical trial evaluating treatment for recurrent uterine cancer (Funding: NRG-GY035). To further amplify the impact of Center members’ investigator initiated trials, CT is leading the UNMCCC Translational Science Initiative (TSI) to enhance the translation of UNMCCC scientific findings to clinical and community interventions.

Research Accomplishments and Scientific Highlights:

• Nanoscience-enabled immune therapy
• Innovative cell therapy platforms for cancer prevention and treatment (also Aim 3)
• Oncolytic immunotherapy
• Targeted therapeutics (also Aim 1 and 3)
• Discovery of GPER/ER-selective ligands and advancement to phase II/III trials (also Aims 1 and 3)
• Combination immune therapy for ovarian cancer evaluated in two national trials (also Aim 3)

Aim 3: Translate UNMCCC discoveries to clinical and community interventions aligned with the needs of our catchment area. Strategic engagement with the other UNMCCC Research Programs, CWGs, and CPDM amplifies the translation of the CT Program’s discoveries into interventional trials. Ongoing collaborations with CMO and CCPS are sustained by prioritizing the integration of correlative studies in clinical protocols to validate mechanisms of action and identify predictive biomarkers of response. Major accomplishments include the successful translation to multi-site, first-in-human, phase I/II trials that have subsequently advanced to national phase II trials [Funding: NCT04130516, NCT06624644, and NRG-GY021; NCT04034927; Prossnitz and Adams). Three new multi-site interventional IITs testing novel prevention and treatment strategies for endometrial cancer have also been opened through the Route66 SPORE (Funding: NCIP50CA265793, Leslie, MPI).

Research Accomplishments and Scientific Highlights:

• Targeted therapeutics (also Aim 1 and 2)
• Discovery of GPER/ER-selective ligands and advancement to phase II/III trials (also Aims 1 and 2)
• Combination immune therapy for ovarian cancer evaluated in two national trials (also Aim 2)
• Development of a multi-site therapeutic IIT for leukemia
• NCORP leadership enhances UNMCCC IITs to address catchment needs in breast cancer diagnosis and treatment